Miniaturization has become a major goal for a wide variety of purposes. An area of great activity has been the synthesis of oligomers, both oligonucleotides and oligopeptides. By having large arrays of different oligomers, one can screen compositions in a variety of ways. For example, with oligonucleotides, one can screen a composition for homologous sequences or complementary sequences. In this way, one can determine the presence of homologous sequences, one can sequence a nucleic acid sequence, and one can identify a pattern of binding which can be associated with an individual, such as a strain, person, plant, or the like. With oligopeptides, there is the opportunity to screen for specific binding proteins which have high affinities to a particular oligopeptide.
The interest in large arrays has been furthered by the continued efforts to improve labels. Thus, as fluorescent and chemiluminescent labels have been developed which provide for high sensitivity, one has the opportunity to detect increasingly smaller amounts of materials. Also, in many instances, one may only have a very small amount of material in a sample, particularly in a complex mixture of materials, so that it becomes desirable to have a small amount of a highly concentrated reagent, so that the complementary member is also highly concentrated.
In providing for large arrays of small dots, there are a number of considerations. The dots should be substantially reproducible in size, particularly if one wishes to quantitate an analyte. Secondly, in the past, it was frequently found that the droplet was associated with satellite droplets, which separated from the main spot and could contaminate other spots, confusing the assay. Third, the device employed, if it is to have commercial acceptance, must be readily filled, be reliable in producing droplets, be easily cleaned, and be reproducible in performance.
U.S. Pat. No. 4,877,745 describes a piezo jet for providing small droplets to produce an assay array. The operation of the device is not particularly convenient, and the droplets are reported to be in the range of 100 pL to 1 .mu.L with the size of the spot made by each droplet being approximately 0.001-0.012 inches in diameter. Schena et al., Science (1995) 270:467-470, describe the preparation of dot arrays for analysis.